Comparison of cardiotoxicity of two anthracenediones and doxorubicin in rats

Two new anthracenediones with antineoplastic activities resembling those of the anthracycline antibiotics were studied in a rat cardiotoxicity model system. NCS-196473 was approx. 10-fold less toxic than doxorubicin and caused only minor electrocardiogram (ECG) changes. Its dihydroxyanalog NSC-279836 was somewhat more toxic than doxorubicin, caused marked leukopenia and induced ECG changes and moderate elevation of serum GOT, LDH and creatine phosphokinase (CK). Both anthracenediones induced marked alterations of mitochondrial structure in the heart but no dilatation of the sarcoplasmic reticulum and distortion of the contractile elements. It is concluded that the cardiotoxic effects of the anthracenediones are of a less specific nature than those caused by doxorubicin.